Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cleaning of human tumor cell lines from arginine-dependent nonfermentative Mycoplasma orale 1 (MO1) by a recently developed technique profoundly altered several in vitro properties of the cell lines. Four melanoma lines (Mel I, Mel St, Mel K, IGR3) and 1 ovarian carcinoma line (Ro) induced human leukocyte interferon (IFN-alpha) only in the mycoplasma-infected state and not in the mycoplasma-free state. MO1-infected tumor lines were generally more susceptible to natural killer (NK) cell-mediated lysis than their mycoplasma-free counterparts. Reinfection of cleaned tumor lines with MO1 restored their interferonogenicity and the increased susceptibility to NK lysis. Thus, the amplifying role of MO1 infection on NK target lysis occurred in connection with an increased production IFN-alpha during the assay period. The human erythroleukemia cell line K562 was exceptional in that it also induced high levels of IFN in an apparently mycoplasma-free state and was unaffected in its susceptibility ot NK lysis by infection with MO1. Possible implications of these findings for the biologic significance of the NK reaction are discussed.
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PMID:Mycoplasma contamination in human tumor cell lines: effect on interferon induction and susceptibility to natural killing. 719 12

The spreading and colonization of tumor cells require their migration to metastatic sites via blood vessels. To penetrate blood-vessel walls, cells, including malignant ones, must recognize and associate with the sub-endothelium extracellular matrix (ECM) and its glycoproteins. Recognition of ECM-glycoproteins, such as fibronectin (FN) and vitronectin (VN), is mediated by integrin receptors expressed on various cell types, including platelets, leukocytes and tumor cells. The Arg-Gly-Asp (RGD)-containing peptide, a major adhesive ligand of ECM, is present in various plasma and matrix glycoproteins, such as FN and VN. Non-peptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear atom spacer, express a high affinity for the alpha IIb-beta 3 integrin and inhibit platelet aggregation. Herein, the ability of RGD mimetics to inhibit adhesive interactions between tumor cells and RGD, and tumor progression in vivo, was examined. RGD-containing peptides and the RGD mimetic, compound SF-6,5, but not the Arg-Gly-Glu (RGE) peptide or the corresponding mimetic, specifically inhibited B16-F10 melanoma cell adhesion to immobilized VN and FN. Daily administration in vivo of SF-6,5 to mice inhibited the formation of B16-F10 colonies in experimental and spontaneous models of metastases. Moreover, SF-6,5 could prevent mouse death caused by massive colonization of tumor cells in the lungs. The therapeutic effect of RGD-containing peptides on tumor metastasis formation was marginal, probably due to the small amounts used, and its susceptibility to proteolysis in situ. Thus, non-peptidic mimetics of small adhesive epitopes may provide a novel therapeutic tool to prevent an adverse pathological event involving integrin-dependent cell-cell and cell-ECM interactions.
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PMID:Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. 750 56

The purpose of these studies was to determine whether the induction of NO synthase activity in murine K-1735 melanoma cells correlated with their metastatic potential. Nonmetastatic, metastatic, and somatic cell hybrids (produced by fusion of nonmetastatic and metastatic cells) were injected i.v. into syngeneic C3H/HeN mice. Metastatic cells survived to produce experimental lung metastases, whereas nonmetastatic cells did not. The various clones and somatic cell hybrids were incubated in vitro with combinations of tumor necrosis factor, interleukin 1, gamma-interferon, and lipopolysaccharide. Nonmetastatic cells exhibited high levels of inducible NO synthase activity and NO, whereas metastatic cells did not. Both the cytotoxic effects of the cytokines and NO production were inhibited by the addition of NG-monomethyl-L-arginine, a specific inhibitor of NO synthase. These data demonstrate an inverse correlation between production of endogenous NO and the ability of K-1735 cells to survive in syngeneic mice to produce lung metastases.
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PMID:Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. 750 36

Maintenance of blood flow is an important factor in sustaining tumour growth. Functional studies have previously demonstrated a reduction in tumour blood flow with selective inhibitors of nitric oxide (NO) synthesis, L-NAME (NG-nitro-L-arginine-methylester) and L-NMMA (NG-monomethyl-L-arginine), when administered locally to tumours derived from murine colon 26 adenocarcinoma and B16 melanoma cells. The type of NO synthase which might be responsible for this locally-derived NO and the site of synthesis was not described. Here we have investigated the distribution of immunoreactivity and the biochemical characteristics of the enzymes synthesizing NO in the same murine model. Adenocarcinoma (colon 26) or melanoma (B16) cells were introduced into a sponge matrix implanted subcutaneously in mice. After 7, 12, and 14 days, the implants were removed and frozen sections were immunostained with rabbit antisera to constitutive and inducible isoforms of NO synthase. Immunoreactivity with antisera to inducible NO synthase was detected in the vasculature of neoplastic implants, with and without the sponge, at 12 and 14 days. The enzyme was not evident in 7-day-old tumours, in non-neoplastic implants, in areas of tissue outside the tumour, or in adenocarcinoma or melanoma cells. Enzyme activity was measurable in homogenates of neoplastic implants removed at day 7 and was found to be Ca2+/calmodulin-independent. Immunoreactivity with antisera to inducible NO synthase was seen principally in the endothelium of newly-formed capillaries, identified by immunostaining for von Willebrand factor in serial sections. Immunoreactivity with antiserum to constitutive NO synthase was not evident in either neoplastic or non-neoplastic implants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. 752 46

Using whole viable human colon carcinoma HT29 cells as immunogen, we produced a monoclonal antibody (mAb) termed 69-6-5. The antibody was functionally selected on its anti-cell-spreading activity. By immunoprecipitation of surface radiolabeled cell lysates from HT29-D4 cells (an HT29 cell clone), mAb 69-6-5 recognized a molecular complex resembling integrin heterodimers. Sequential immunodepletions with mAb to the integrin alpha v subunit demonstrated that this complex was composed of alpha v-containing integrins. Accordingly, mAb 69-6-5 reacted with integrin alpha v beta 3 immunopurified from melanoma cells and integrins alpha v beta 5 and alpha v beta 6 immunopurified from pancreatic carcinoma cells. In cell adhesion assays, the 69-6-5 mAb was able to inhibit strongly in a dose-dependent manner arginine-glycine-aspartic acid-mediated adhesion of HT29-D4 cells to vitronectin, fibronectin, or ProNectin F but not to laminin or collagen. Immunoprecipitations with beta chain-specific antisera indicated that these cells express integrins alpha v beta 5 (receptor for vitronectin) and alpha v beta 6 (receptor for fibronectin) but neither alpha v beta 1 nor alpha v beta 3. In summary, these results indicated that mAb 69-6-5 reacts with several alpha v integrins and that it can effectively interfere with the adhesive functions of at least alpha v beta 5 and alpha v beta 6, which represent the major receptors on HT29-D4 cells responsible for their adhesion on vitronectin and fibronectin.
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PMID:A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins alpha v beta 3, alpha v beta 5, and alpha v beta 6. 751 10

Cell-adhesion activity of the bovine propolypeptide of von Willebrand factor (pp-vWF) was assessed by means of an in vitro assay with several cell lines of both normal and tumor-cell origin. pp-vWF promoted adhesion and spreading of B16 mouse melanoma cells and G-361 human melanoma cells. However, it could not induce adhesion of any other cell lines tested including endothelial cells, normal fibroblasts, and tumor cells of sarcoma, carcinoma, neuroblastoma and leukemia origin. A monospecific polyclonal antibody against pp-vWF, but not against fibronectin, laminin, and von Willebrand factor (vWF), completely blocked the pp-vWF-mediated adhesion, indicating that the cell adhesion was due to the pp-vWF molecule and not due to possible contamination of these three well-known adhesive proteins. The cell-adhesion activity was also observed with human pp-vWF and, furthermore, the adhesion to both bovine and human pp-vWF was not affected by a peptide containing the Arg-Gly-Asp sequence while the peptide abolished the cell adhesion to vWF. The adhesion was completely dependent on Mg2+ and inhibited by Ca2+. Inhibition by an anti-(beta 1 integrin) mAb (4B4) indicates that the receptor for this protein belongs to the beta 1-integrin family. A monoclonal antibody (TC4) among several antibodies directed against bovine pp-vWF inhibited the B16 adhesion to immobilized pp-vWF. The epitope for this monoclonal antibody lies in a central 8-kDa portion of pp-vWF, suggesting that this region is important for the cell-adhesion activity. This idea was supported by the finding that purified 8-kDa fragment promoted adhesion of B16 cells in a concentration-dependent manner. As pp-vWF shows unique cell-type specificity in its adhesion activity, which is completely different from that of fibronectin, laminin, vWF and collagen, it may be a novel type of adhesive glycoprotein that utilizes a beta 1-integrin receptor.
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PMID:Beta 1-integrin-mediated adhesion of melanoma cells to the propolypeptide of von Willebrand factor. 751 67

Previous studies from our laboratory demonstrated an inverse relationship between the expression level of inducible nitric oxide synthase (iNOS) and the metastatic potential of murine K-1735 melanoma cells. The purpose of this study was to provide direct evidence that the expression of iNOS suppresses metastatic potential of melanoma cells. Highly metastatic K-1735 clone 4 cells (C4.P), which express low levels of iNOS, were transfected with a functional iNOS (C4.L8), inactive-mutated iNOS (C4.S2), or neomycin-resistance (C4.Neo) genes in medium containing 3 mM NG-methyl-L-arginine (NMA). Positive transfectants were identified by Southern and Northern blot analyses and homogeneous staining with a specific anti-iNOS monoclonal antibody. Semiconfluent cultures of C4.P (parental), C4.Neo.3 (control transfection), C4.S2.3 (inactive iNOS), and C4.L8.5 (functional iNOS) were harvested, and viable cells were injected intravenously into syngeneic C3H/HeN mice and allogeneic BALB/c nude mice. C4.P, C4.Neo.3, and C4.S2.3 cells were highly metastatic whereas C4.L8.5 cells were not metastatic. Experiments with [125I]dUrd-labeled tumor cells demonstrated that the initial arrest in the lung microvasculature did not differ among the lines, but that C4.L8.5 cells died by 48-72 h after injection. Enhanced survival of all K-1735 C4 cells (including C4.L8.5) was found in mice given twice daily injections of 20 mg NMA. The C4.L8.5 cells produced slow growing subcutaneous tumors in nude mice, whereas the other three lines produced fast growing tumors. In vitro studies confirmed that in the absence of NMA the expression of iNOS in C4.L8.5 cells induced apoptosis. Collectively, these data demonstrate that the expression of recombinant iNOS in melanoma cells is associated with apoptosis, suppression of tumorigenicity, and abrogation of metastasis.
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PMID:Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. 753 33

We investigated the role of nitric oxide (NO) in the expression of interleukin-8 (IL-8) in the human melanoma cell line, G361. Three NO donors, 3-morpholinosydnonimine hydrochloride (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), and S-nitroso-L-glutathione (SNOG), all caused an increase in both IL-8 protein secretion and promoter activity. Truncation of the promoter showed that 101 bp of the 5' flanking region proximal to the transcription start site are sufficient for the response to NO. Furthermore, mutation of the NF-kappa B and NF-IL-6 binding sites led to a significant decrease in NO-stimulated promoter activity. The nitric oxide synthase inhibitor, NG-amino-L-homoarginine (NAHA), inhibited TNF-alpha-stimulated IL-8 promoter activity by 60%. Addition of excess L- but not D-arginine partially reversed the NAHA-mediated inhibition. These results demonstrate that NO is an endogenous regulator of IL-8 production in G361 melanoma cells.
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PMID:Nitric oxide regulates IL-8 expression in melanoma cells at the transcriptional level. 757 68

Since the adhesive interaction between tumor cells and host cells, or extracellular matrix (ECM), presumably plays a crucial role in metastatic formation, we used synthetic or recombinant polypeptide analogues, poly (RGD), CH-271 or SCM-chitin-RGDS based on Arg-Gly-Asp (RGD) sequence. Poly (RGD) effectively inhibited the experimental lung and liver metastasis when coinjected i.v. with different types of tumors. In a spontaneous lung metastasis model using B16-BL6 melanoma, multiple administrations of this polypeptide, before or after surgical excision of the primary tumor, resulted in significant inhibition of tumor metastasis. The mechanism responsible for the inhibition is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the process of metastasis. CH-271 fusion polypeptide was much more effective in inhibiting lung or liver metastasis of tumors than cell-binding domain (C-274) or heparin-binding domain (H-271) polypeptides. SCM-chitin-RGDS conjugate significantly reduced the number of tumor colonies in the lungs by coinjection with Colon 26 carcinoma as compared with either RGDS or SCM-chitin alone. Since the polypeptides derived from cell adhesion molecules showed no toxicity to the host, they may provide a promising approach for the control of cancer metastasis.
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PMID:[Inhibition of tumor metastasis by synthetic peptide analogues of cell-adhesive RGD sequence of fibronectin]. 763 3

Integrins are a class of adhesion molecules that depends on divalent cations for proper function. This study examined whether human normal melanocytes and malignant (metastatic) melanocytes with early and late stages of cellular differentiation (G361 and SK-MEL-23, respectively) would differ in integrin-mediated adhesion to fibronectin, laminin, as well as collagens type I and type IV, and whether divalent cations could influence the strength of adhesion ability. Integrin subunit expression was determined by flow cytometry using integrin subunit-specific antibodies as probes. Integrin-specific adhesion was determined using soluble glycine-arginine-glycine-asparagine-serine peptide and integrin subunit-specific antibodies as functional blocking agents. This study shows that both normal and malignant melanocytes adhere to extracellular matrices in a divalent cation-dependent manner, and adhesion strength varies with the cation species. Integrins can be rapidly activated by small alterations in cation concentration, manganese being the most potent. There were marked differences in substrate adhesion between normal melanocytes and metastatic malignant melanoma cells, but these differences were not related to the stage of cellular differentiation. All the three cell types, however, expressed the same integrin subunits at approximately the same levels. This suggests that substrate adhesion of melanocytes and melanoma cells might involve some integrin-independent mechanisms as well. Manganese, in particular, appears to cause adhesion by activating both integrin-dependent and -independent mechanisms.
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PMID:Divalent cations control cell-substrate adhesion and laminin expression in normal and malignant human melanocytes in early and late stages of cellular differentiation. 763 17


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